The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports ....The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports a role for EV as key players in innate immunity, a full understanding of the biological relevance of these vesicles and how they serve as a cellular defence mechanism is lacking. This project will provide significant benefits such as addressing key questions in EV biology and providing new fundamental insights into a novel and poorly understood component of the innate immune response.Read moreRead less
Intraepithelial lymphocyte development and function in the intestine. This study aims to better understand the homeostatic maintenance and essential repair processes in the intestine. This project will generate new knowledge of how immune cells of the intestine, known as intraepithelial lymphocytes (IELs), engage with intestinal epithelial cells, neurons and commensal microbes to promote homeostasis and repair. Expected outcomes of this project will be identification of new molecules for future ....Intraepithelial lymphocyte development and function in the intestine. This study aims to better understand the homeostatic maintenance and essential repair processes in the intestine. This project will generate new knowledge of how immune cells of the intestine, known as intraepithelial lymphocytes (IELs), engage with intestinal epithelial cells, neurons and commensal microbes to promote homeostasis and repair. Expected outcomes of this project will be identification of new molecules for future drug and vaccine development to improve gut health and vaccination in mammals. This should provide significant benefits to the Australian population and livestock industry through improved protection against cancer, intestinal infections and increased productivity. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101300
Funder
Australian Research Council
Funding Amount
$423,711.00
Summary
Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills inva ....Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills invading bacteria via newly discovered structures made by dying macrophages called extracellular traps. Insight we gain by interrogating this immune cell signalling pathway, called the non-canonical inflammasome, will add valuable knowledge to our fundamental understanding of mammalian inflammation and anti-microbial responses
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Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic ....Regulation of lung immune-epithelial networks sensing environmental change. This study aims to uncover how lung epithelial cells engage with immune cells and determine their cellular and molecular wiring to ensure homeostatic maintenance and essential repair processes of lung tissues. Maintenance of lung epithelial-immune networks is essential to maintain normal lung tissue structure and function, and to induce immune responses to protect against microbial challenges or inhaled potentially toxic substances. Understanding this molecular program of epithelial-immune cell-mediated sensing/repair will be essential to understand how tissue-repair processes can be driven in the lung, an organ critical for respiration and thus life.Read moreRead less
Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that h ....Deciphering novel cross-talk between innate cytokine receptors. Understanding the basic functions of interferons, how they signal to cells, is central to understanding fundamental immunity. Interferons are crucial molecules of the immune system that are important for normal cell development and they protect the body from viral infection and cancer but can be deleterious in different autoimmune diseases and trauma settings. Preliminary Data shows there is a pathway of interferon signalling that has previously been overlooked. This project aims to understand how this pathway works and how it contributes to the normal workings of cells. This fundamental science has future consequences for the design of vaccines and for the design of therapeutics to treat diseases that show defective interferon signalling.Read moreRead less
An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the r ....An investigation into CD1a, a versatile antigen-presenting molecule. This project aims to investigate how T lymphocytes are activated by lipids presented by the skin-associated antigen-presenting molecule, CD1a. Using X-ray crystallography and cellular immunology, we will provide fundamental insight into this poorly understood immunological axis. We will determine the molecular basis for how CD1a presents diverse self and foreign lipids, and how such CD1a-lipid complexes are recognised by the responding T cells. This basic science discovery project will provide substantial new knowledge in the burgeoning field of lipid-mediated immunity, which should ultimately lead to new therapies targeting the CD1a lipid display molecule to either prevent immune mediated damage or promote protective immunity as required.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100823
Funder
Australian Research Council
Funding Amount
$442,482.00
Summary
Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is acti ....Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is activated, it induces the release of messenger substances to alert other immune cells. This research will deliver fundamental knowledge of how animals normally co-exist with microbes.Read moreRead less
Why do neutrophils swarm? This project aims to combine novel immunology, microscopy and computational approaches to investigate how immune cells called neutrophils cooperate to protect the host against microbes. Neutrophils are rapidly recruited to sites of inflammation and then utilise a type of highly coordinated collective behaviour termed swarming. However, the role of neutrophil swarms in fighting off infection is poorly understood. The project is poised to generate new knowledge on the imp ....Why do neutrophils swarm? This project aims to combine novel immunology, microscopy and computational approaches to investigate how immune cells called neutrophils cooperate to protect the host against microbes. Neutrophils are rapidly recruited to sites of inflammation and then utilise a type of highly coordinated collective behaviour termed swarming. However, the role of neutrophil swarms in fighting off infection is poorly understood. The project is poised to generate new knowledge on the importance of immune cell cooperation by developing in silico models of the immune response. The project will provide benefit through enhanced understanding of fundamental principles of immunity and develop new computational tools to model complex immune function in silico.Read moreRead less